Erythrocyte-ghost integrated gold nanostars for synergistic therapy in hypoxic tumors
A.V. Karmenyan1*, W.G. Pearl1, R. Selvam1, H.Y. Lee2, T.E. Hsu1, E.V. Perevedentseva3, H.H. Chang2, S.Y. Wu1, C.L. Cheng1
1-Department of Physics, National Dong Hwa University, Hualien 97401, Taiwan 2- Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien 97004, Taiwan 3- P.N. Lebedev Physics Institute of Russian Academy of Sciences, Moscow, 119991, Russia
* artashes@gms.ndhu.edu.tw
Modern lasers provide wide variety of radiation parameters. This makes it possible to select conditions for their multifunctional use for diagnostics and combined treatment. In the present work gold nanostars (AuNSt) are tested as promising agents for dual photo-based therapies, combining photodynamic therapy (PDT) and photothermal therapy (PTT) to tackle a cancer. In cases where tumors exhibit low oxygen levels, making them resistant to conventional therapies, PDT utilizes light to generate reactive oxygen species (ROS), inducing oxidative damage to cancer cells, while PTT leverages light to produce heat, destroying the tumor microenvironment. In this study, AuNSt with a plasmon absorption peak at 800 nm were synthesized [1] and loaded onto erythrocyte ghosts. Containing residual hemoglobin erythrocyte ghosts were utilized as oxygen supplements and carriers to overcome the hypoxic environment of tumors. The AuNSt facilitated enhanced ROS production and exhibited photothermal conversion efficiency under near-infrared (NIR) irradiation. Application of AuNSt@Ghost in various cell lines under normoxic and hypoxic conditions, exposed to NIR irradiation, demonstrated a significant synergistic antitumor effect. This biomimetic approach shows promise in theranostics, offering a viable strategy for treating cancers with improved efficacy and reduced systemic toxicity.
AuNSt Ghost
AuNSt@Ghost
400
(c)
500 600 700 Wavelength (nm)
800
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Value Standard Error
B Intercept -34.313 2.38604
Slope 207.231 1.29968
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tj)
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_i_i_i_i_i_TmeJsl__7 .
Time (min)
Fig. 1. (a) SEM image of AuNSt; (b) UV-Vis absorption spectra of AuNSt, Ghost, and AuNSt@Ghost; (c) Linear-time data showing the negative natural logarithm of the temperature driving force obtained during the cooling stage of AuNSt. Inset: Heating-cooling cycle of AuNSt solution; and (d) The rate constant for the AuNSt sample, measured by 2'7'-dichlorofluorescein absorbance changes at 410 nm caused by ROS generated from AuNSt under 808 nm laser irradiation.
[1] W.G. Pearl, E.V. Perevedentseva, A.V. Karmenyan, V.A. Khanadeev, S.Y. Wu, Y.R. Ma, N.G. Khlebtsov, C.L. Cheng, Multifunctional
plasmonic gold nanostars for cancer diagnostic and therapeutic applications, J Biophotonics, e202100264 (2021).